Congenital primary hypothyroidism with subsequent adenomatous goiter in a Turkish patient caused by a homozygous 10-bp deletion in the thyroid peroxidase (TPO) gene.

Objective: Congenital primary hypothyroidism occurs in 1 of 4000 births. Whereas the majority of the cases are due to developmental defects of the thyroid gland, 20% carry a defect in thyroid hormonogenesis. We report a Turkish boy who had goitrous hypothyroidism due to a mutation in the thyroid peroxidase (TPO) gene.

Design: The TPO gene was sequenced directly from genomic DNA and cDNA which was transcribed from three RNA samples harvested from different parts of the patient's excised thyroid gland. Patient The boy was thyroidectomized because of continuing growth of his thyroid gland and development of multiple nodes suspected of malignancy by ultrasound examination. Histopathological examination verified a dyshormonogenetic goiter with multiple follicular adenomas.

Results: The patient had a novel homozygous 10-bp deletion of the TPO gene at position 2812 in exon 16. This frame shift mutation results in a severely altered intracellular part of the protein. The deletion identified in leucocyte DNA was also found in thyroid tissue cDNA - so that instability of the transcript or a splicing defect was excluded. Both unaffected parents were heterozygous carriers of the mutation whereas 50 healthy individuals of the same ethnic background did not harbour the mutation.

Conclusions: The identified TPO gene deletion is the first mutation coding for an inactive TPO molecule, which has a severely altered intracellular segment. Because the most likely reason for the enlarging goiter was poor compliance of the patient, this report underlines the importance of a careful and regular follow-up of patients with dyshormonogenesis.